What changed in this filing

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Item 2. Management’s Discussion and Analysis

2022-11-10 compared with 2022-08-04 · 82 added, 77 removed, 237 unchanged (40% of the section changed)

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In preclinical studies we observed meaningful transgene expression in both the CNS and in peripheral organs affected in GM1.

We are conducting clinical trials using an intra-cisterna magna, or ICM, method of administration, which involves an injection at the craniocervical junction.

We are conducting a clinical trial using an intra-cisterna magna, or ICM, method of administration, which involves an injection at the craniocervical junction.

We have an active IND, or Investigational New Drug application, from the U.S.

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In the fourth quarter of 2021, we reported initial safety and 30-day biomarker data from the initial cohort of two late onset patients with GM1 treated with the low dose of PBGM01.

We also reported interim safety data for the initial cohort that showed PBGM01 was well tolerated with no serious adverse events and no evidence of dorsal root ganglion toxicity.

In February 2022 and May 2022, we reported meaningful developmental improvement in assessments, utilizing the Bayley III and Vineland II scales, performed by trained healthcare providers and the patients’ caregivers, respectively, for both patients in the initial cohort.

Additionally, we have dosed our first patient in Cohort 2, for late onset infantile GM1 with high dose PBGM01, and completed dosing patients in Cohort 3, for early onset infantile GM1 with low dose PBGM01.

Initial biomarker and safety data from Cohort 2 and Cohort 3 are expected to be reported in the second half of 2022.

The safety data showed PBGM01 was well tolerated with no serious adverse events and no evidence of dorsal root ganglion toxicity.

In early 2022, we reported increases in cerebrospinal fluid, or CSF, and serum b -gal activity above baseline with sustained activity up to one year in the initial cohort.

In addition, meaningful developmental improvement was reported in assessments, utilizing the Bayley III and Vineland II scales, performed by trained healthcare providers and the patients’ caregivers, respectively, for both patients in the initial cohort.

We have now completed dosing patients in Cohort 2, for late onset infantile GM1 with high dose PBGM01, and Cohort 3, for early onset infantile GM1 with low dose PBGM01.

Additionally, we have dosed our first patient in Cohort 4, for early onset infantile GM1 with high dose PBGM01, and expect to dose the final patient in Cohort 4 in the fourth quarter of 2022.

Initial biomarker and safety data from Cohort 2 and Cohort 3 are expected to be reported in December of 2022.

The FDA has granted Orphan Drug Designation, or ODD, Rare Pediatric Disease Designation, or RPDD, and Fast Track Designation, to PBGM01 for the treatment of GM1.

The European Commission has granted Orphan designation for PBGM01.

The European Commission has granted Orphan designation and Advanced Therapy Medicinal Product, or ATMP, designation for PBGM01.

Through our manufacturing partners, we have manufactured the PBGM01 clinical supply and have established a clinical supply chain to support global clinical trials.

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We selected the AAV1 capsid and ICM administration for PBFT02 because this approach led to extensive and robust expression of human PGRN throughout the brain and spinal cord of NHPs, and due to the higher PGRN levels in CSF using AAV1 as compared with other serotypes tested.

ICM administration of AAV1 to NHPs resulted in CSF levels of human PGRN in excess of 50-fold higher than those in healthy human subjects’ CSF, and in excess of 5-fold higher than levels achieved in NHPs with AAVhu68 or AAV5.

ICM administration of AAV1 to NHPs resulted in CSF levels of human PGRN in excess of 50-fold

higher than those in healthy human subjects’ CSF, and in excess of 5-fold higher than levels achieved in NHPs with AAVhu68 or AAV5.

We have an active IND from the FDA and approved CTAs in multiple countries for PBFT02, which allows us to proceed with our upliFT-D Trial, an international, multi-center, open-label, single-arm Phase 1/2 clinical trial of PBFT02 in patients with a diagnosis of early symptomatic FTD-GRN.

We expect to dose the first patient in our initial cohort of our upliFT-D Trial in mid-2022.

In August 2022, we dosed the first patient in our upliFT-D trial.

The FDA has granted ODD and Fast Track Designation to PBFT02 for the treatment of FTD-GRN and the European Commission granted Orphan designation for PBFT02.

Through our manufacturing partners, we have manufactured the PBFT02 clinical supply to support clinical trial initiation.

Through our manufacturing partners, we have manufactured the PBFT02 clinical supply and have established a clinical supply chain to support global clinical trials.

PBKR03 for the Treatment of Krabbe disease

We are currently developing PBKR03, which utilizes a proprietary, next-generation AAVhu68 capsid to deliver to the brain and peripheral tissues a functional GALC gene encoding the hydrolytic enzyme galactosylceramidase for Krabbe disease.

We have rights to PBKR03, which utilizes a proprietary, next-generation AAVhu68 capsid to deliver to the brain and peripheral tissues a functional GALC gene encoding the hydrolytic enzyme galactosylceramidase for Krabbe disease.

Krabbe disease is an autosomal recessive lysosomal storage disease caused by mutations in the GALC gene, which provides instructions for making an enzyme called galactosylceramidase, which breaks down certain fats, including galactosylceramide and psychosine.

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We have an active IND from the FDA and approved CTAs in multiple countries for PBKR03, which allows us to proceed with our GALax-C Trial, an international, multi-center, open-label, single-arm Phase 1/2 clinical trial of PBKR03 in patients with a diagnosis of infantile Krabbe disease.

The FDA has granted ODD, RPDD, and Fast Track Designation to PKBR03, and the European Commission granted Orphan designation for PBKR03.

In March 2022, we dosed the first patient in our GALax-C Trial.

T his patient experienced a grade 4 adverse event of acute communicating hydrocephalus, which is a build-up of the CSF in the brain, twenty-six days after dosing.

Health authorities, including the FDA and ex-U.S.

regulatory agencies, as well as study investigators, were notified per regulatory requirements.

The patient underwent surgery to have a shunt inserted to reduce CSF build-up in the brain.

The procedure was well-tolerated, and the patient has been stable post-procedure.

Following an investigation, this adverse event was assessed to be possibly related to either study treatment or study procedures due to the temporal proximity of the adverse event to the administration of treatment.

At the time of the adverse event, there was no evidence of inflammation in blood or in cerebrospinal fluid.

However, the role of disease progression may also be a factor due to the following findings:

1) hydrocephalus has been reported in the literature in association with Krabbe disease, and 2) baseline imaging showed evidence of changes in the ventricles of the brain that progressed following dosing in this patient.

In addition, preliminary biomarker data in this patient showed rapid normalization of GALC activity and reduction of psychosine in both serum and CSF within 30 days.

The Independent Data Monitoring Committee, or IDMC, recommended continuation of the trial with specified modifications including certain changes to the inclusion/exclusion criteria and additional monitoring post administration.

The protocol has been updated and submitted to relevant health authorities and ethics committees.

In addition, per study protocol, we have also increased the number of subjects in Cohort 1 from three to four following this adverse event.

We are proceeding with study recruitment, and we expect to report interim safety and biomarker data from a subset of Cohort 1 by the end of 2022.

The FDA has granted ODD, RPDD, and Fast Track Designation to PKBR03, and the European Commission granted Orphan designation for PBKR03.

Through our manufacturing partners, we have manufactured PBKR03 clinical supply to support clinical trial initiation.

On subsequent MRI examinations, the acute hydrocephalus was completely resolved.

PBKR03 has been otherwise well tolerated with no other adverse events related to study treatment and no evidence of dorsal root ganglion toxicity or cell-mediated immune response.

Through our manufacturing partners, we have manufactured PBKR03 clinical supply and have established a clinical supply chain to support global clinical trials.

In November 2022, we announced plans to stop further clinical development of PBKR03 for Krabbe disease due to prioritization of resources and intend to explore strategic alternatives to advance this program.

PBML04 for the Treatment of Metachromatic Leukodystrophy

We are developing PBML04, which utilizes a proprietary, next-generation AAVhu68 capsid to deliver to the brain and peripheral tissues a functional arylsulfatase A gene, or ARSA, encoding the ARSA enzyme for Metachromatic Leukodystrophy, or MLD.

MLD is a rare, autosomal recessive lysosomal storage disease caused by mutations in the ARSA gene, resulting in little or no functional activity of the ARSA enzyme, which is essential for the degradation of sphingolipid cerebroside-3-sulfate, or sulfatide.

We have the rights to develop PBML04, which utilizes a proprietary, next-generation AAVhu68 capsid to deliver to the brain and peripheral tissues a functional arylsulfatase A gene, or ARSA, encoding the ARSA enzyme for Metachromatic Leukodystrophy, or MLD.

sphingolipid cerebroside-3-sulfate, or sulfatide.

Sulfatides are the most abundant sphingolipids in myelin and have important structural and functional roles in the maintenance of myelin.

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On May 20, 2022, the FDA cleared our IND application for PBML04, which allows us to proceed with PBML04-001, an international, multi-center, open-label, single-arm clinical trial of PBML04 in patients with a diagnosis of late onset infantile MLD.

As we continue to evaluate our resources and operating expenses, we have made the decision to hold advancement of clinical development activities for the MLD program at this time.

Through our manufacturing partners, we have manufactured PBML04 clinical supply to support clinical trial initiation.

We have made the decision to hold advancement of clinical development activities for the MLD program at this time due to prioritization of resources and intend to explore strategic alternatives to advance this program.

Research Programs

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We also have exploratory research programs with GTP for large indications, initially focused on Alzheimer’s Disease, or AD, and Temporal Lobe Epilepsy, or TLE, which can be expanded to other large CNS diseases upon mutual agreement with GTP.

In November 2022, we stopped further advancement of our exploratory research program in AD.

Business Overview

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Since inception, we have devoted substantially all of our resources to acquiring and developing product and technology rights, conducting research and development, organizing and staffing our company, business planning, and raising capital.

We have incurred recurring losses, the majority of which are attributable to research and development activities, and negative cash flows from

We have incurred recurring losses, the majority of which are attributable to research and development activities, and negative cash flows from operations.

Historically, we have funded our operations through the sale of convertible preferred stock and public offerings of common stock.

Our net loss was $39.5 and $48.4 million for the three months ended June 30, 2022 and 2021, respectively, and $82.4 million and $87.3 million for the six months ended June 30, 2022 and 2021, respectively.

As of June 30, 2022, we had an accumulated deficit of $438.6 million.

Our net loss was $26.7 and $46.9 million for the three months ended September 30, 2022 and 2021, respectively, and $109.1 million and $134.2 million for the nine months ended September 30, 2022 and 2021, respectively.

As of September 30, 2022, we had an accumulated deficit of $465.3 million.

Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative expenditures.

Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current or future product candidates.

We expect to continue to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through all stages of development and clinical trials and, ultimately, seek regulatory approval.

In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution.

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In March 2022, we announced a 13 percent reduction in workforce and plans to prioritize research and development programs, as described above, to reduce operating expenses and to extend our cash runway.

We have slowed our investment in our pilot plant and therefore, the establishment of a pilot plant will be later than end of 2022.

As of June 30, 2022 , we had cash, cash equivalents and marketable securities of $239.3 million.

We expect our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2024.

In November 2022, we announced a further 23 percent reduction in workforce and plans to prioritize research and development programs to reduce operating expenses and to extend our cash runway.

As of September 30, 2022, we had cash, cash equivalents and marketable securities of $213.8 million.

We expect our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the first half of 2025.

COVID-19 Impact

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The safety and well-being of employees, patients and partners is our highest priority.

As we diligently work to activate sites for our clinical programs, we are experiencing some impacts to our site initiation activities related to COVID-19, such as meeting delays with various investigational review bodies or ethics committees that have prioritized COVID-19 related clinical trials and staffing levels at site hospitals.

As we diligently work to activate sites for our clinical programs, we have experienced some impacts to our site initiation activities related to COVID-19, such as meeting delays with various investigational review bodies or ethics committees that have prioritized COVID-19 related clinical trials and staffing levels at site hospitals.

For example, the clinical initiation of our upliFT-D clinical study for PBFT02 and the GALax-C clinical study for PBKR03 were substantially impacted by COVID-19-related issues.

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We have a research, collaboration and licensing agreement, as amended, or the Penn Agreement, with Penn, for research and development collaborations and exclusive license rights to patents for certain products and technologies.

Penn Agreement, we have the obligation to fund certain research relating to the preclinical development of selected products in research programs as well as the new exploratory research program in non-rare and/or non-monogenic (or large) CNS indications, initially AD and TLE.

Under the Penn Agreement, we have the obligation to fund certain research relating to the preclinical development of selected products in research programs as well as the new exploratory research program in non-rare and/or non-monogenic, or large CNS indications, initially AD and TLE.

We also fund discovery research conducted by Penn through August 2026 and will receive exclusive rights, subject to certain limitations, to technologies resulting from the discovery program for products developed with GTP, such as novel capsids, toxicity reduction technologies and delivery and formulation improvements.

Our discovery research funding commitment is $5.0 million a year for five years, with quarterly payments of $1.3 million through June 2026.

Under the Penn Agreement we have eight remaining options available to us to commence additional licensed programs for CNS indications until May 2026.

Under the Penn Agreement we have eight remaining options available to us

to commence additional licensed programs for CNS indications until May 2026.

If we were to exercise any of these remaining options, we would owe Penn a non-refundable aggregate fee of $1.0 million, with $0.5 million per product indication paid immediately and another $0.5 million fee owed upon a further developmental milestone.

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Under the exploratory research program, we will have the right to further develop and commercialize any gene therapy product candidates specific for those selected targets within AD and TLE (and any future large CNS indications that are mutually agreed upon) that arise from the exploratory research programs on substantially the same terms of the current Penn Agreement.

In November 2022, we stopped further advancement of our exploratory research program in AD.

Collaboration and Manufacturing and Supply Agreements

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The Collaboration Agreement continues to be in effect pursuant to its terms .

Under the terms of the Manufacturing and Supply Agreement, Catalent has agreed to manufacture batches of drug product for our gene therapy product candidates at the Clean Room

Suite provided for in the Collaboration Agreement.

Under the terms of the Manufacturing and Supply Agreement, Catalent has agreed to manufacture batches of drug product for our gene therapy product candidates at the Clean Room Suite provided for in the Collaboration Agreement.

There is a minimum annual purchase commitment owed to Catalent for five years beginning in November 2020, subject to certain inflationary adjustments.

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General and Administrative Expenses

General and administrative expenses consist primarily of personnel expenses, including salaries, benefits and share-based compensation expense, for employees and consultants in executive, finance, accounting, legal, information

technology, commercial, quality, regulatory, operations and human resource functions.

General and administrative expenses also include corporate facility costs, including rent, utilities, depreciation and maintenance, not otherwise included in research and development expenses, legal expenses related to intellectual property and corporate matters, insurance expense, and expenses for accounting and consulting services.

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Results of Operations

Comparison of the Three Months Ended June 30, 2022 and 2021

The following table sets forth our results of operations for the three months ended June 30, 2022 and 2021:

Comparison of the Three Months Ended September 30, 2022 and 2021

The following table sets forth our results of operations for the three months ended September 30, 2022 and 2021:

Three months ended

September 30,

(in thousands)

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Research and Development Expenses

Research and development expenses decreased by $6.3 million to $26.8 million for the three months ended June 30, 2022 from $33.1 million for three months ended June 30, 2021.

The decrease was primarily due to a decrease of $10.9 million in clinical manufacturing expenses, which relates to the timing of our manufacturing activities.

This amount was partially offset by a $1.2 million increase in research and development expenses associated with the Penn Agreement, a $1.6 million increase in facility and other expenses, a $1.6 million increase in clinical operations and professional fee expenses, and a $0.2 million increase in personnel-related and share-based compensation expenses.

Personnel-related and share-based compensation expenses for the three months ended June 30, 2021 includes $0.9 million of expenses related to modifications of shared-based compensation awards, compared to no modifications of share-based compensation awards for the three months ended June 30, 2022.

Research and development expenses decreased by $11.2 million to $15.4 million for the three months ended September 30, 2022 from $26.6 million for three months ended September 30, 2021.

The decrease was primarily due to a decrease of $8.8 million in clinical manufacturing expenses, which relates to the timing of our manufacturing activities to support our clinical trials;

a decrease of $1.8 million in personnel-related and share-based compensation expense;

a decrease of $1.0 million in clinical operations and professional fees related to start-up costs incurred for our clinical trials in the three months ended September 30, 2021;

and a decrease of $0.3 million in research and development expenses associated with the Penn Agreement.

These amounts were partially offset by a $0.7 million increase in facility and other expenses.

Expenses associated with the Penn Agreement will continue to vary from quarter to quarter based on our selection and prioritization of preclinical product candidates, the status of our preclinical pipeline and timing of preclinical work performed.

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Three months ended

September 30,

(in thousands)

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Acquired In-Process Research and Development Expenses

During both of the three months ended June 30, 2022 and 2021, we incurred no expenses related to the achievement of development milestones.

During the three months ended September 30, 2022, we incurred $1.5 million of expenses related to the achievement of a development milestone.

During the three months ended September 30, 2021, we incurred $0.5 million in expenses related to license fees and $5.0 million in fees related to the exploratory research program amendment with Penn.

General and Administrative Expenses

General and administrative expenses decreased by $2.4 million to $13.0 million for the three months ended June 30, 2022 from $15.4 million for three months ended June 30, 2021.

The decrease was primarily due to a $2.3 million decrease in personnel-related and share-based compensation expense related to our workforce reduction, which was partially offset by severance expenses incurred in the three months ended June 30, 2022 related to the resignation of our Chief Executive Officer, and a $0.1 million decrease in our professional fees, facilities and other expenses.

General and administrative expenses decreased by $4.3 million to $10.7 million for the three months ended September 30, 2022 from $15.0 million for three months ended September 30, 2021.

The decrease was primarily due to a $4.0 million decrease in personnel-related and share-based compensation expense related to our March 2022 workforce reduction and a $0.4 million decrease in our professional fees, facilities and other expenses.

Interest Income, net

Interest income, net was $0.3 million and $0.1 million for the three months ended June 30, 2022 and 2021, respectively, and were primarily attributable to interest income earned on cash, cash equivalents and marketable securities, partially offset by realized losses on marketable securities in the three months ended June 30, 2022.

Comparison of the Six Months Ended June 30, 2022 and 2021

The following table sets forth our results of operations for the six months ended June 30, 2022 and 2021:

Six Months Ended

Interest income, net was $0.8 million and $0.2 million for the three months ended September 30, 2022 and 2021, respectively, and was primarily attributable to interest income earned on cash, cash equivalents and marketable securities.

Comparison of the Nine Months Ended September 30, 2022 and 2021

The following table sets forth our results of operations for the nine months ended September 30, 2022 and 2021:

Nine Months Ended

September 30,

(in thousands)

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Research and Development Expenses

Research and development expenses decreased by $5.0 million to $53.0 million for the six months ended June 30, 2022 from $58.1 million for six months ended June 30, 2021.

The decrease was primarily due to a decrease of $5.7 million in clinical manufacturing expenses, a $4.0 million decrease in research and development expenses associated with the Penn Agreement, and a $1.3 million decrease in personnel-related and share-based compensation.

These decreases were partially offset by a $3.2 million increase in clinical operations and professional fees expense and a $2.8 million increase in facility and other expense.

Research and development expenses decreased by $16.3 million to $68.4 million for the nine months ended September 30, 2022 from $84.7 million for nine months ended September 30, 2021.

The decrease was primarily due to a decrease of $14.6 million in clinical manufacturing expenses, which relates to the timing of our manufacturing activities to support our clinical trials;

a $4.6 million decrease in research and development expenses associated with the Penn Agreement;

and a $3.1 million decrease in personnel-related and share-based compensation, which primarily relates to share-based compensation modification expense recognized in the nine months ended September 30, 2021.

These amounts were partially offset by a $2.6 million increase in clinical operations and professional fees expense and a $3.4 million increase in facility and other expense.

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Research and development expenses are summarized by program in the table below:

Six Months Ended

Nine Months Ended

September 30,

(in thousands)

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Acquired In-Process Research and Development Expenses

During both of the six months ended June 30, 2022 and 2021, we incurred expenses of $1.5 million related to the achievement of a development milestone.

During the nine months ended September 30, 2022, we incurred expenses of $3.0 million related to the achievement of development milestones.

During the nine months ended September 30, 2021, we incurred $0.5 million in expenses related to license fees, $1.5 million related to the achievement of a development milestone, and $5.0 million in fees related to the exploratory research program amendment with Penn.

General and Administrative Expenses

General and administrative expenses increased by $0.2 million to $28.1 million for the six months ended June 30, 2022 from $27.9 million for six months ended June 30, 2021.

The increase was primarily due to a $0.8 million increase in personnel-related and share-based compensation expense.

Personnel-related and share-based compensation expense includes modifications of share-based compensation and severance related expenses incurred during the six months ended June 30, 2022, which was partially offset by lower personnel-related expenses due to our workforce reduction.

This amount was also partially offset by a $0.6 million decrease in professional fees, facility and other expenses.

General and administrative expenses decreased by $4.1 million to $38.8 million for the nine months ended September 30, 2022 from $42.9 million for the nine months ended September 30, 2021.

The decrease was primarily due to a $3.3 million decrease in personnel-related and share-based compensation expense, which relates to our March 2022 workforce reduction and a $0.8 million decrease in professional fees, facility and other expenses.

Interest Income, net

Interest income, net $0.3 million and $0.2 million for the six months ended June 30, 2022 and 2021, respectively, and were primarily attributable to interest income earned on cash, cash equivalents and marketable securities, partially offset by realized losses on marketable securities in the six months ended June 30, 2022

Interest income, net was $1.1 million and $0.3 million for the nine months ended September 30, 2022 and 2021, respectively, and was primarily attributable to interest income earned on cash, cash equivalents and marketable securities.

Liquidity and Capital Resources

As of June 30, 2022, we had $239.3 million in cash, cash equivalents and marketable securities and had an accumulated deficit of $438.6 million.

We expect that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the second quarter of 2024.

As of September 30, 2022, we had $213.8 million in cash, cash equivalents and marketable securities and had an accumulated deficit of $465.3 million.

We expect that our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditure requirements into the first half of 2025.

Funding Requirements

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Until such time, if ever, as we can generate substantial product revenue, we expect to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements.

liquidation or other preferences that adversely affect existing stockholders’ rights as common stockholders.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, existing stockholders’ ownership interests will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect existing stockholders’ rights as common stockholders.

Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making acquisitions or capital expenditures or declaring dividends.

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The following table shows a summary of our cash flows for the periods indicated:

Six Months Ended

Nine Months Ended

September 30,

(in thousands)

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Net Cash Used in Operating Activities

During the six months ended June 30, 2022, we used $70.8 million of net cash in operating activities.

During the nine months ended September 30, 2022, we used $94.2 million of net cash in operating activities.

Cash used in operating activities reflected a net loss of $109.1 million and a net increase in our operating assets of $7.5 million, partially offset by non-cash charges of $22.4 million related to share-based compensation, depreciation, amortization of premium and discount, net, and acquired in-process research and development.

The primary use of cash was to fund our operations related to the development of our product candidates.

During the six months ended June 30, 2021, we used $55.0 million of net cash in operating activities.

Cash used in operating activities reflected a net loss of $87.3 million, which was partially offset by net increase in our operating net liabilities of $9.5 million and non-cash charges of $21.2 million related to share-based compensation, depreciation, amortization of premium and discount, net, and changes in deferred rent.

During the nine months ended September 30, 2021, we used $96.1 million of net cash in operating activities.

Cash used in operating activities reflected a net loss of $134.2 million, which was partially offset by net increase in our operating net liabilities of $1.3 million and non-cash charges of $36.8 million related to share-based compensation, depreciation, amortization of premium and discount, net, changes in deferred rent and acquired in-process research and development.

The primary use of cash was to fund our operations related to the development of our product candidates.

Net Cash Used in Investing Activities

During the six months ended June 30, 2022, we purchased $58.8 million in marketable securities, had sales and maturities of $95.3 million in marketable securities, had purchases of property and equipment of $1.6 million, and paid $1.5 million for technology licenses.

During the six months ended June 30, 2021, we purchased $132.1 million in marketable securities, had sales and maturities of $108.3 million in marketable securities, had purchases of property and equipment of $4.8 million, and paid $2.0 million for technology licenses.

Net Cash Provided by (Used) in Investing Activities

During the nine months ended September 30, 2022, we purchased $116.3 million in marketable securities, had sales and maturities of $149.7 million in marketable securities, purchased $1.8 million of property and equipment, and paid $3.0 million for technology licenses.

During the nine months ended September 30, 2021, we purchased $169.9 million in marketable securities, had sales and maturities of $146.0 million in marketable securities, purchased $10.8 million of property and equipment, and paid $7.5 million for technology licenses.

Net Cash Provided by (Used in) Financing Activities

During the six months ended June 30, 2022 , we received $49,000 from the exercise of stock options, received $0.2 million in proceeds from the issuance of common stock under the ESPP and paid $0.6 million for short-term insurance premium financing.

During the six months ended June 30, 2021, we received net proceeds of $165.8 million from the sale of our common stock, received $0.2 million from the exercise of stock options and received $0.5 million in proceeds from the issuance of common stock under the ESPP.

During the nine months ended September 30, 2022 , we received $0.1 million from the exercise of stock options, received $0.2 million in proceeds from the issuance of common stock under the ESPP and paid $1.1 million for short-term insurance premium financing.

During the nine months ended September 30, 2021, we received net proceeds of $165.8 million from the sale of our common stock, received $0.2 million from the exercise of stock options and received $0.5 million in proceeds from the issuance of common stock under the ESPP.

We also paid $0.3 million in deferred offering costs.

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Critical Accounting Policies and Estimates

During the six months ended June 30, 2022, there were no material changes to our critical accounting policies and estimates from those described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Estimates” in our 2021 Annual Report filed on Form 10-K.

During the nine months ended September 30, 2022, there were no material changes to our critical accounting policies and estimates from those described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Estimates” in our 2021 Annual Report filed on Form 10-K.

JOBS Act Accounting Election

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis